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Identification of novel resistance mechanisms against clofazimine in Mycobacterium tuberculosis.

Increasing resistance of Mycobacterium tuberculosis to antibiotics plays a crucial role in the current epidemiology of tuberculosis (TB). Because of, amongst others, inadequate treatment of multi-drug resistant (MDR) TB - with resistance to isoniazid and rifampicin - the incidence of extreme-drug resistant (XDR) TB - defined as MDR-TB with additional resistance to fluoroquinolones (FQ) and one of the injectable second-line antibiotics - worldwide.Clinical studies show that the use of FQs is necessary for successful MDR-TB treatment. Clofazimin (CLOF) is also being used more and more in the standard treatment of MDR-TB. Clinical CLOF-resistant M. tuberculosis isolates have been poorly described to date and the resistance mechanisms are insufficiently known. It is suspected that CLOF provides an increased release of lysophospholipids on the one hand and superoxide and hydrogen peroxide on the other, resulting in bacterial cell death. The molecular mechanism behind the potential effect of CLOF is not well known, but efflux pumps may play a role in resistance.The proposed study aims to identify new resistance mechanisms for two antibiotics that form the pillars of MDR-TB treatment.
Date:1 Jul 2013  →  30 Jun 2017
Disciplines:Microbiology, Systems biology, Laboratory medicine, Tropical medicine
Project type:Collaboration project